Treponema pallidum (T. pallidum) is the microaerophilic spirochete that causes syphilis, a systemic venereal disease with multiple clinical presentations. Other closely related treponemes cause pinta (Treponema carateum), yaws (Treponema pallidum subspecies pertenue), and bejel (Treponema pallidum subspecies endemicum).
In 1996 over 11,000 cases of primary and secondary syphilis in the United States were reported to the U.S. Centers for Disease Control and Prevention. The initial infection causes an ulcer at the site of infection; however, the bacteria move throughout the body, damaging many organs over time. Although treatment with penicillin in the early stages may be successful, the early symptoms of syphilis can be very mild, and many people do not seek treatment when they first become infected. This delay in seeking treatment is harmful because the damage to the organs in late syphilis cannot be reversed. Also of increasing concern is the risk of transmitting and acquiring the human immunodeficiency virus (HIV) that causes AIDS via open ulcers caused by syphilis.
Medical experts describe the course of the syphilis disease by dividing it into stages: primary, secondary, latent, and tertiary (late). An infected person who has not been treated may infect others during the first two stages, which usually last one to two years. The bacteria spread from the initial ulcer of an infected person to the skin or mucous membranes of the genital area, the mouth, or the anus of a sexual partner. The bacteria can also pass through broken skin on other parts of the body. In its late stages, untreated syphilis, although not contagious, can cause serious heart abnormalities, mental disorders, blindness, other neurologic problems, and even death.
The first symptom of primary syphilis is an ulcer called a chancre. The chancre can appear within 10 days to three months after exposure, but it generally appears within two to six weeks. The chancre is usually found on the part of the body exposed to the partner's ulcer, such as the penis, the vulva, or the vagina. A chancre also can develop on the cervix, tongue, lips, or other parts of the body. Because the chancre may be painless and may occur inside the body, it may go unnoticed. Although the chancre disappears within a few weeks whether or not a person is treated, if the infection is not treated during the primary stage, about one-third of those infected will progress to the chronic stages of syphilis.
Secondary syphilis is often marked by a skin rash that is characterized by brown sores about the size of a penny. The rash appears anywhere from three to six weeks after the chancre appears. While the rash may cover the whole body, the palms of the hands and soles of the feet are the most common sites of presentation. Because active bacteria are present in these sores, any physical contact, sexual or nonsexual, with the broken skin of an infected person may spread the infection at this stage. The rash usually heals within several weeks or months. Other symptoms may also occur such as mild fever, fatigue, headache, sore throat, patchy hair loss, and swollen lymph glands throughout the body. These symptoms may be very mild and, like the chancre of primary syphilis, will disappear without treatment.
The signs of secondary syphilis may come and go over the next one to two years. If untreated, syphilis may lapse into a latent stage during which the disease is no longer contagious and no symptoms are present. Although many individuals who are not treated will suffer no further consequences of the disease, approximately one-third of those who have secondary syphilis develop the complications of late, or tertiary, syphilis.
In the tertiary stage of syphilis, bacteria damage the heart, eyes, brain, nervous system, bones, joints, or almost any other part of the body. This stage can last for years, or even decades. Late syphilis can result in mental illness, blindness, other neurologic problems, heart disease, and even death.
During the early stages of infection, syphilis bacteria also frequently invade the nervous system, and approximately three to seven percent of persons with untreated syphilis develop neurosyphilis. However, development of neurosyphilis can take up to twenty years and some persons with neurosyphilis never develop any symptoms. Those who do present symptoms may experience headaches, stiff necks, and fever, which result from an inflammation of the lining of the brain. Seizures and symptoms of stroke such as numbness, weakness, or visual problems may also afflict those patients with neurosyphilis. Although neurosyphilis can be treated, treatment may be more difficult and its course may be different in persons infected with HIV.
The effects of syphilis in pregnant women are particularly compelling because of the consequential effects on the unborn child. It is likely that an untreated pregnant woman with active syphilis will pass the infection to her unborn child. About 25 percent of these pregnancies result in stillbirth or neonatal death. Between 40 to 70 percent of such pregnancies will yield a syphilis-infected infant. Some infants with congenital syphilis may have symptoms at birth, but most develop symptoms between two and three weeks post partum. These symptoms may include skin sores, rashes, fever, swollen liver and spleen, jaundice, anemia, and various deformities. Care must be taken in handling an infant with congenital syphilis because the moist sores are infectious. Rarely, the symptoms of syphilis go undetected in infants. As infected infants become older children and teenagers, they may develop the symptoms of late-stage syphilis including bone, tooth, eye, ear, and brain damage.
Due to the sometimes serious and life threatening effects of syphilis infection, and the risk of transmitting or contracting HIV, specific and early diagnosis of the infection is essential. Syphilis, however, has sometimes been called “the great imitator” because its early symptoms are similar to those of many other diseases. Therefore, a doctor usually does not rely upon recognition of the signs and symptoms of syphilis, but performs both microscopic identification of syphilis bacteria and blood tests.
To diagnose syphilis by a microscopic identification of the bacterium, the physician may take a scraping from the surface of the ulcer or chancre and examine it under a special “dark-field” microscope to detect the organism. However, dark-field microscopy requires considerable skill and is prone to misinterpretation. For these reasons, most cases of syphilis are diagnosed serologically. The blood tests most often used to detect evidence of syphilis are the VDRL (Venereal Disease Research Laboratory) test and the RPR (rapid plasma reagent) test. These non-treponemal tests employ natural lipids, cardiolipin and lecithin, to detect antibodies against non-specific antigens during an active syphilitic infection.
However, one of the complaints about the non-treponemal tests is their lack of specificity in comparison to the treponemal tests. Due to the occurrence of false positives and false negatives when using non-treponemal tests, more than one blood test is usually required. The rate of false positives and the need for multiple blood tests is increased in those individuals with autoimmune disorders, certain viral infections, and other conditions involving substantial tissue destruction or liver involvement. Although treponemal-based tests such as the fluorescent treponemal antibody-absorption (FTA-ABS) and the T. pallidum hemagglutination assay (TPHA) may be used to confirm a positive test result, treponemal-based tests are more expensive and more difficult to use than non-treponemal tests. Treponemal tests also cannot be used as tests for cure after treatment because they remain positive even after eradication of the infection.
Some treponemal tests currently in use depend upon the detection of proteins anchored in the T. pallidum cytoplasmic membrane. Detection of such proteins is particularly difficult because of the unusual structure of the T. pallidum membrane, which consists predominantly of lipids that tend to “shield” these proteins from detection. This shielding effect often delays the host's immune response frequently resulting in false negative serological results.
Currently available treponemal tests depend mainly on the detection of antibodies to cytoplasmic membrane anchored lipoproteins. Response to these proteins is typically delayed because of their lack of surface exposure since the outer membrane consists mainly of lipids and is protein poor. The tests often yield confusing and inaccurate results because these lipoproteins are highly antigenic and may be responsible for the long lasting response in treponemal tests. Because of this latter property, treponemal tests cannot differentiate a current versus a past infection.
Syphilis usually is treated with penicillin, administered by injection. Other antibiotics are used for treating patients allergic to penicillin. A patient typically loses the ability to transmit syphilis within 24 hours from initiating therapy. Some infected individuals, however, do not respond to the usual doses of penicillin. Therefore, it is important that patients undergoing treatment for syphilis are monitored through periodic blood tests to ensure that the infectious agent has been completely destroyed. Persons with neurosyphilis may need to be re-tested for up to two years after treatment.
In all stages of syphilis, proper treatment may cure the disease, but in late syphilis, damage already done to body organs cannot be reversed. Screening and treatment of infected individuals, or secondary prevention, is one of the few options available for preventing the advanced stages of syphilis disease. Testing and treatment early in pregnancy is the best way to prevent syphilis in infants and should be a routine part of prenatal care. A vital component in the successful treatment and prevention of syphilis is early and accurate detection of T. pallidum infection.
Diseases Associated with other Treponemal Infections
Pinta, caused by Treponema carateum, has become very rare, and is limited to the warm arid tropical Americas (in particular, Mexico, Central America, and Colombia). The disease manifests in the form of primary and secondary lesions. The primary lesions, which may persist for several years, are coalescing pruritic papules on the extremities, face, neck, chest, or abdomen. The secondary lesions are disseminated small, scaly papules, called pintids. These may become dyschromic (i.e., change from the normal color of the skin). Late lesions are achromic (without pigment).
Bejel, caused by Treponema pallidum subspecies endemicum, is known by many names in local languages as a form of syphilis that is not sexually transmitted and occurs in children. Transmission can be by direct contact, and also (in contradistinction to all the other treponemal diseases) via fomites, as in sharing drinking vessels and eating utensils. Except for the fact that the primary lesion, which is probably in the oral mucosa, is rarely observed, the disease is virtually identical to syphilis, with gummas, condylomata lata, and periostitis.
Yaws, caused by Treponema pallidum subspecies pertenue, occurs in warm, humid tropics. Yaws disease also predominantly manifests in the form of lesions. The primary lesion is a papillomatous skin lesion that heals spontaneously, only to be followed by the secondary lesions, which are large papillomatous nodules that are widely distributed over the skin surface. The late stage of the disease is characterized by gummas of various bones and the nasopharynx as well as destruction lesions of the skin, lymph nodes, and bones. The skin over the gummas may ulcerate. The disease is present in primitive tropical areas in parts of South America, Central Africa, and Southeast Asia and is spread by direct contact with infected skin.
Though some treatments for treponemal infection are available, control of treponemal diseases is managed by eliminating person to person spread. Accordingly, early detection of treponemal infection is vital for reducing widespread dissemination of related diseases.
Thus, there remains a need for accurate and improved methods and compositions for the effective, accurate early diagnosis of T. pallidum infection and methods for monitoring T. pallidum therapy.